Antibiotic Susceptibility, Virulome, and Clinical Outcomes in European Infants with Bloodstream Infections Caused by Enterobacterales

Abstract

Mortality in neonates with Gram-negative bloodstream infections has remained unacceptably high. Very few data are available on the impact of resistance profiles, virulence factors, appropriateness of empirical treatment and clinical characteristics on patients’ mortality. A survival analysis to investigate 28-day mortality probability and predictors was performed including (I) infants <90 days (II) with an available Enterobacterales blood isolate with (III) clinical, treatment and 28-day outcome data. Eighty-seven patients were included. Overall, 299 virulence genes were identified among all the pathogens. Escherichia coli had significantly more virulence genes identified compared with other species. A strong positive correlation between the number of resistance and virulence genes carried by each isolate was found. The cumulative probability of death obtained by the Kaplan-Meier survival analysis was 19.5%. In the descriptive analysis, early age at onset, gestational age at onset, culture positive for E. coli and number of classes of virulence genes carried by each isolate were significantly associated with mortality. By Cox multivariate regression, none of the investigated variables was significant. This pilot study has demonstrated the feasibility of investigating the association between neonatal sepsis mortality and the causative Enterobacterales isolates virulome. This relationship needs further exploration in larger studies, ideally including host immunopathological response, in order to develop a tailor-made therapeutic strategy.

Outcomes with Cefiderocol Treatment in Patients with Bacteraemia Enrolled into Prospective Phase 2 and Phase 3 Randomised Clinical Studies

“…Bloodstream infections (BSIs) are an important cause of morbidity and mortality across all ages [ 1 – 4 ]. BSI is a relatively common complication of serious infections [ 5 – 7 ], and outcomes in patients with gram-negative bacteraemia are often poor [ 8 ], particularly when initiation of appropriate antimicrobial therapy is delayed [ 9 – 11 ].…”

The Role of Virulence Factors in Neonatal Sepsis Caused by Enterobacterales: A Systematic Review

“…Four studies reported the association between bacterial VFs and neonatal mortality. One focused the analysis on sepsis due to E. coli [ 11 ], one on Klebsiella pneumoniae [ 5 ], the third analysed both E. coli and K. pneumoniae strains [ 12 ], and the last included a wider group of GNB ( E. coli , Klebsiella spp., Enterobacter spp., Serratia spp./ Proteus mirabilis ) [ 13 ].…”

“…Three studies used a genome-wide approach to investigate the impacts of a pathogen’s determinants on neonatal sepsis morbidity and mortality [ 5 , 12 , 13 ]. Studies investigating the association between number of virulence genes (VGs) and neonatal mortality showed opposite results.…”

Gram-negative bacteria isolates and their antibiotic-resistance patterns among pediatrics patients in Ethiopia: A systematic review

“…Higher resistance rates of these bacteria could be considered as great threats and alarm the stakeholders to have more surveillance and control of the use of antimicrobials to combat infection. 10 – 12 …”

“…Laboratory sample : only human infection sample carried out by the Kirby–Bauer disk diffusion method as per Clinical Laboratory Standards Institute (CLSI) guidelines on Mueller–Hinton agar (Oxoid, Basingstoke, Hampshire, England). 7 , 11 …”